4-Hydroxy-2-nonenal (HNE), one of the cytotoxic aldehydes produced by lipid peroxidation, is an a,b-unsaturated aldehyde that can modify proteins by reacting with the side-chain of cysteine, histidine, and lysine residues. The reaction of HNE and lysine derivatives were studied in order to gain some knowledge of the protein modification process. From the mixture of reaction products, a fluorescent compound could be isolated in very low yield. This fluorophore exhibited spectroscopic properties very similar to those observed for lipofuscin, the age pigment. Thus, its structural elucidation could shed some light on the chemical nature of lipofuscin. The mass spectral data of this fluorophore indicated that the molecule was derived from two molecules of acetyllysine and one molecule of HNE with the loss of four hydrogen atoms, i.e. an oxidative process. An analogous fluorophore could be obtained when HNE was reacted with other acyllysine, suggesting that the formation of the fluorophore did not involve the a-amino acid portion of the lysine molecule. Indeed, similar fluorophores were formed from HNE with g-aminobutyric acid and b-alanine, respectively. However, with glycine, no fluorophore formation was observed. Therefore, the minimum requirement for the fluorophore formation was an aminoethylene chain in the molecule. The fluorophores produced in these reactions were in general rather stable in acid but would decompose readily under basic conditions. The carboxylic acid functions were readily esterified, but other chemical transformations were unsuccessful. The NMR data thus far were not definitive due to insufficient material; hence, an assignment of structure is as yet not amenable. However, the spectroscopic properties and the mode of the reaction suggest a general feature of the structure as being a conjugated triene or a cyclic diene.